1. Local and Circuit Resting-State Activity Predict Brain Activation and Behavioral Performance of Working Memory We examined the relationship between intrinsic brain activity at rest and evoked activity during a task using resting-state and task-driven N-back working memory (WM) task functional MRI data collected in the same session. Using fractional amplitude of low frequency fluctuations (fALFF) as an index of local resting-state activity, we found that fALFF in the middle frontal gyrus and inferior/superior parietal lobule were positively correlated with WM task induced activation, while fALFF in the superior frontal gyrus was negatively correlated with WM task induced deactivation. Using resting-state functional connectivity (rsFC) as an index of circuit resting-state activity, we showed that the rsFC between frontal and parietal cortices were significantly correlated with WM task activation. Further, we found that the relationship between the resting-state activity and task-evoked activation was stronger at higher task loads. In addition, both resting-state activity and the task-induced activation were significantly correlated with the behavioral performance of the WM task. 2. Convergent Evidence that Cocaine Alters Medial Prefrontal Regions Structure and Function We investigated the structural and functional alterations in chronic cocaine users (CU) and compared to match healthy controls (HC). Specifically, cortical thickness and amplitude of low-frequency fluctuation (ALFF) were examined for 39 CUs and compared to 39 HCs. The correlations between the structural and functional indices to the years of cocaine use were evaluated in the CU group. Three regions were found to have significantly reduced cortical thickness in the CU group: left medial and superior frontal gyrus, right superior frontal gyrus, and right middle and superior temporal gyrus. In the CU group, cortical thickness was significantly correlated to use year with a negative coefficient in medial and superior prefrontal regions. Decreased fALFF was found in the medial and prefrontal cortex and dACC in the frequency band over 0.001 - 0.027 Hz. 3. Relationship between Working Memory Task Activation and Fractional Volume of Gray Matter BOLD functional MRI is a widely used neuroimaging method;however, significant inter-subject variations in BOLD response have been shown. In the current study, we hypothesize that the potential differences in fractional volume of gray matter (fv,GM) of the same brain area across subjects could be a source of inter-subject variations in BOLD response. To test this hypothesis, a voxel-wise, intersubject correlation analysis was performed between BOLD responses from a parametric working memory task and fv,GM measured by a fast fractional signal mapping from inversion recovery (FRASIER) technique. Our results showed inter-subject correlations between fv,GM and WM induced BOLD activations, both in the task activated and deactivated regions. Further investigations showed that statistical power for detecting brain activation was improved using fv,GM as a covariate. These results indicate that variations of inter-subject tissue fraction (such as fv,GM) account significantly for the variations in BOLD responses to the WM task in specific brain regions. 4. TE-Dependent Spatial and Spectral Specificity of Functional Connectivity Spatial and spectral characteristics of functional connectivity were examined using a multiple gradient-echo sequence at 3T. In spatial domain, we found broad, local correlations at short echo times (TE 14 ms) due to dominant spin density (S0) contribution, whereas long-range connections mediated by transverse relaxation time (T2*) became explicit at TEs longer than 22 ms. In the frequency domain, compared with the flat spectrum of S0, spectral power of the T2*-weighted signal elevated significantly with increasing TE, particularly in the frequency ranges of 0.008-0.023 Hz and 0.037-0.043 Hz. Using S0 spectrum as a reference, we proposed two indices to measure spectral signal change (SSC) and spectral contrast-to-noise ratio (SCNR), respectively, for quantifying RS-fMRI signal. The two indices demonstrated TE dependencies of connectivity-related fluctuation strengths, resembling functional contrasts in activation-based fMRI. These findings confirmed further that large scale functional connectivity based on the BOLD mechanism is constrained within specific frequency ranges in every brain network, and the spectral features of S0 and T2* could be useful for interpreting and quantifying RS-fMRI data. 5. Diffeomorphic Image Registration of Diffusion MRI Using Spherical Harmonics Most current diffusion MRI registration techniques are limited to the alignment of diffusion tensor imaging (DTI) data. We propose a novel diffeomorphic registration method for high angular resolution diffusion images by mapping their orientation distribution functions (ODFs). ODFs can be reconstructed using q-ball imaging (QBI) techniques and represented by spherical harmonics (SHs) to resolve intra-voxel fiber crossings. The registration is based on optimizing a diffeomorphic cost function. Unlike scalar images, deforming ODF maps requires ODF reorientation to maintain its consistency with the local fiber orientation. Our method simultaneously reorients the ODFs by computing a Wigner rotation matrix at each voxel, and applies it to the SH coefficients during registration. The proposed method was validated on both simulated and real data sets. Results show that the diffeomorphic registration improved the affine alignment, and registration using SHs with higher order SHs further improved the registration accuracy by reducing the shape difference and improving the directional consistency of the registered and reference ODF maps. 6. Proton magnetic resonance spectroscopy techniques to detect neurotransmitters in humans Proton magnetic resonance spectroscopy (MRS) provides a powerful tool for in vivo neurochemical quantification of the brain. Editing MRS techniques, which are dedicated to detect one or two neurotransmitters with the suppression of other metabolites, achieve cleaner signal background and thus better quantifications than ultra-short TE MRS. One of the editing techniques, difference spectroscopy, was developed and implemented on our human scanners. The quantification methods for GABA and Glu were explored. Currently a project to study the correlation between GABA/Glu levels and fMRI signals is in progress. Several projects using the editing technique for GABA/Glu measurements in psychiatric disorders are proposed and currently in the preparation phase. 7. The influence of carbon dioxide on brain activity and metabolism in conscious humans This study investigates how an increase in blood CO2, via inhalation of 5% CO2, may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO2) by 13.4% 2.3% (N=14) and, furthermore, the CMRO2 change was proportional to the subject's end-tidal CO2 (Et-CO2) change. Using functional connectivity MRI (fcMRI) to assess the resting-state neural activity, the hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visual-evoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO2 inhalation.